In carriers of the BRCA1 gene mutation, researchers have found vitamin D biosynthesis and signaling to be impaired. This study provides a viable reason to explore the potential use of vitamin D in treatments to prevent ovarian cancer in women with the BRCA1 mutation.
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At this point in time, there is only one nutrient in the human body that can be generated via exposure to sunlight. Vitamin D is not only biologically produced by UV light; it can also be metabolized by eating oily fish, such as salmon and tuna, mushrooms, eggs, dairy products, and other vitamin D fortified foods and supplements. In addition to its role in regulating calcium, this steroid hormone has other functions in the body—including important regulatory effects on cell proliferation.
“Vitamin D (VD) regulates the expression of genes involved in the major hallmarks of cancer [18].”
Epithelial Ovarian Cancer and BRCA1 Mutations
The BRCA1 gene functions to maintain genomic stability and acts as a tumor suppressor by regulating DNA repair, chromatin reorganization, transcription, and ubiquitination. While there have been studies of epithelial ovarian cancer (EOC), the researchers recognized an elevated need to study ovarian cancer patients with BRCA1 mutations (BRCA1mut). A lack of early-detection of EOC has led to poor outcomes for the majority of patients that are eventually diagnosed with this disease.
Previous epidemiological studies have suggested an inverse correlation between vitamin D levels and the risk of breast and ovarian cancer. In patients who had BRCA1mut breast cancer, vitamin D receptors (VDR) were absent and inversely associated with cancer development. Receptors of vitamin D have been found in, among other regions, the ovaries and fallopian tubes—both origins of EOC. This suggests a possible relationship between vitamin D signaling and cancer development in BRCA1mut carriers.
“Women with inherited mutations in BRCA1 gene have a high (40–70%) genetic risk of developing ovarian cancer.”
The Study
Researchers from Oregon Health & Science University and Northern Arizona University conducted an in vitro study to analyze the levels and actions of vitamin D in samples of blood, ovary, and fallopian tubes in healthy premenopausal women with and without the BRCA1 mutation. They examined whether vitamin D supplementation can regulate the expression of vitamin D receptors and the proliferation of ovarian surface epithelial cells taken from healthy carriers of the BRCA1 mutation.
“Considering the regulatory effects of VD on cell proliferation, we investigated the potential for VD in the prevention of EOC in BRCA1mut carriers. We sought to determine circulating VD levels and VDR expression in ovarian surface epithelial (OSE)/fallopian tube epithelial (FTE) cells in healthy women with BRCA1mut.”
Concentrations of vitamin D circulating in the samples were measured by an electrochemiluminescence immunoassay. To determine vitamin D receptor expression, researchers performed immunohistochemistry on ovarian and fallopian tube samples. They cultured ovarian surface epithelial cells from the BRCA1mut carriers with and without calcitriol, or biologically active vitamin D, supplementation for 72 hrs. The team then analyzed vitamin D receptor expression, protein levels, cell proliferation, and cell viability.
Results
“BRCA1mut women had lower serum calcifediol [circulating vitamin D] levels compared to BRCAwt women [without the mutation]. VDR protein expression was evident in ovarian and the fallopian tube epithelium of BRCAwt patients, but was reduced in BRCA1mut women.”
In their study, vitamin D supplements elevated vitamin D receptor expression in cultured BRCA1mut samples and decreased cell proliferation in a dose-dependent manner without inducing programmed cell death.
Conclusion
“Vitamin D treatment may limit BRCA1mut epithelial cell proliferation without affecting cell viability, providing a rationale for exploring the potential for VD in ovarian cancer prevention in BRCA1mut carriers.”
Click here to read the full scientific paper, published in Oncotarget.
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